Diaphragmatic Peritonectomy and Full-Thickness Resection in CRS/HIPEC May Allow Higher Completeness of Cytoreduction Rates with a Low Rate of Respiratory Complications.

BACKGROUND: Cytoreductive surgery (CRS) provides a survival benefit when achieved without residual disease. As diaphragm is frequently affected in peritoneal malignancies, complete cytoreduction often requires surgical techniques over the diaphragm. The purpose of the study was to assess diaphragmatic resection impact on cytoreduction completeness, morbidity and mortality compared to less aggressive diaphragmatic peritonectomy in CRS and hyperthermic intraperitoneal chemotherapy (HIPEC) settings. MATERIALS AND METHODS: Patients with peritoneal carcinomatosis and supramesocolic disease undergoing CRS/HIPEC from 2011 to 2019 were included in a prospectively collected database. We compared patients who underwent full-thickness diaphragmatic resection (DR) and diaphragmatic peritonectomy (DP). Epidemiological and clinical data, morbidity, and mortality within 90 days of surgery were documented. RESULTS: 232 patients were initially selected. Inclusion criteria were met by 88 procedures. DR was performed on 32 patients and DP on 56. Number of resected organs was 5.21 in the DR cohort vs. 3.57 in the DP cohort (p<0.0001). Rate of Peritoneal Cancer Index (PCI) score >14 was higher in the DR group (75%) than in the DP group (50.9%) (p=0.027). Tumor invasion of diaphragmatic muscle after DR was confirmed in 89.3% patients. Postoperative pleural effusion was observed in 28 patients (50%) in the DP group and in 17 (53.1%) in the DR group. CONCLUSIONS: CRS/HIPEC requires specific surgical techniques over the diaphragm to achieve complete cytoreduction. As diaphragmatic muscle invasion is frequent, full-thickness resection may allow a cytoreduction completeness increase without an increased morbidity. Pleural drains are not systematically required as these procedures show low incidence of major respiratory complications.

Prophylactic HIPEC with oxaliplatin might be of benefit in T4 and perforated colon cancer: another possible interpretation of the COLOPEC results.

The COLOPEC trial failed to show evidence for improved relapse-free survival (RFS) between the two study groups: 80,9% (95% CI 73.3-88.5) in the experimental group and 76.2 % (68.0-84.4) in the control group (one-sided log-rank p = 0.28). Nevertheless only 87 patients received the adjuvant HIPEC treatment in the experimental arm (n = 100). This group had a peritoneal relapse of 19 %, but only 10 % had a truly peritoneal relapse as 9 of them had stablished peritoneal carcinomatosis and 1 case was a peritoneal recurrence but did not receive adjuvant HIPEC. We conducted a per-protocol analysis comparing the 87 patients which truly received the adjuvant HIPEC to the 102 patients in the control arm and obtained an OR 0.396 (95 % CI 0.17-0.91) with a (Pearson Chi-Square p = 0.026, two-tailed Fisher exact test p = 0.032). This contradicts the COLOPEC reported conclusions and shows that adjuvant HIPEC could have an important protective role against peritoneal recurrence.

Secondary surgical cytoreduction needs to be assessed taking into account surgical technique, completeness of cytoreduction, and extent of disease.

Recent evidence suggested that secondary surgical cytoreduction followed by chemotherapy does not result in longer overall survival in patients with platinum-sensitive recurrent ovarian cancer.This statement is based on a phase III multicenter, randomized clinical trial that lacks a description of the surgical protocol, the surgical technique, and the surgical variables. In a study that evaluates surgical cytoreduction, it is mandatory to assess the grade of cytoreductive surgery achieved (Sugarbaker PH, Langenbeck's Arch Surg 384:576-87, 1999), the extent of disease using PCI (Peritoneal Cancer Index), the technique itself, and the existence of a multidisciplinary approach with extensive upper abdominal procedures in experienced centers (Ren et al, BMC Cancer 15:1-12, 2015). There is evidence proving that the quality of cytoreduction (Al Rawahi et al, Cochrane Database Syst Rev 2013, 2013), the measurement of the amount of disease by PCI (Elzarkaa et al, J Gynecol Oncol 29, 2018), and a multidisciplinary approach with supramesocolic procedures (Ren et al, BMC Cancer 15:1-12, 2015) impact overall survival.This study fails to compare chemotherapy with secondary cytoreductive surgery since, due to the lack of variables, we can assess neither the performed surgery nor its criteria. This study should not be taken into account to recommend chemotherapy alone over a surgical approach in this group of patients.

Current practice in cytoreductive surgery and HIPEC for metastatic peritoneal disease: Spanish multicentric survey.

INTRODUCTION: Radical Cytoreductive Surgery (CRS) with Hyperthermic Intraperitoneal Chemotherapy (HIPEC), has been proposed as the current standard of treatment for metastatic peritoneal disease by several tumors. Despite its widely utilization, there seems to be a great variability in their organization, clinical practice, and safety among centers. AIM OF THE STUDY: To obtain updated information on clinical practice in different perioperative areas of the CRS-HIPEC. PATIENTS AND METHODS: All 25 members of the Spanish Surface Peritoneal Malignancy (GECOP), were invited to answer an online survey, to describe their usual practice in different perioperative areas of the CRS-HIPEC. RESULTS: Survey was responded by 100% of centers. This study represents more than 800 patients treated annually. Seventy per cent of respondents perform CRS-HIPEC for more than 5 years. The most frequent technique was Coliseum (88%). Routinely non-invasive monitoring of cardiac output is used by 92% of centers. More than 50% of centers administer oxaliplatin (74%), or mitomycin-C (65%) in colorectal cancer; cisplatin in gastric cancer (73%) and mesothelioma (74%). Ovarian cancer is treated with cisplatin and various combinations, in 64% or paclitaxel in 54.5%. Spillage protocol was available in 100% centers. CONCLUSIONS: Data showed an important variability in volume of patients per center, selection of cytostatic agents, professional training and safety measures applied. The standardization of CRS/HIPEC procedures based on the best available evidence, the individualization of patients and the consensus among professionals, constitute an important part of the basis that will allow us to improve results of this complex procedure.

From utopia to reality: increased survival in peritoneal carcinomatosis treated with cytoreduction and hyperthermic intraperitoneal chemotherapy.

We have read with great interest the article by Illán et al.1 entitled "Long survival in a patient with metastatic colorectal carcinoma: reality or utopia?" This article describes the case of a 42 year old patient with mucinous-type colon adenocarcinoma who had tumor recurrence with peritoneal metastases 18 months after resection of the primary tumor and adjuvant chemotherapy. After multiple metastasectomies and several lines of chemotherapy, the patient died 27 months after the recurrence.

Influence of simultaneous liver and peritoneal resection on postoperative morbi-mortality and survival in patients with colon cancer treated with surgical cytoreduction and intraperitoneal hyperthermic chemotherapy. / Influencia de la resección hepática y peritoneal simultánea, en la morbimortalidad y supervivencia de los pacientes con cáncer de colon intervenidos mediante cirugía citorreductora con quimioterapia intraperitoneal hipertérmica.

INTRODUCTION: Cytoreductive surgery plus intraperitoneal hyperthermic chemotherapy (HIPEC) has recently been established as the treatment of choice for selected patients with peritoneal carcinomatosis of colonic origin. Until recently, the simultaneous presence of peritoneal and hepatic dissemination has been considered a contraindication for surgery. The aim of this paper is to analyze the morbidity, mortality and survival of patients with simultaneous peritoneal and hepatic resection with HIPEC for peritoneal carcinomatosis secondary to colon cancer. METHODS: Between January 2010 and January 2015, 61 patients were operated on, 16 had simultaneous peritoneal and hepatic dissemination (group RH+), and 45 presented only peritoneal dissemination (group RH-). RESULTS: There were no differences between the groups in terms of demographic data, length of surgery and extension of peritoneal disease. Postoperative grade III-V complications were significantly higher in the RH+ group (56.3 vs. 26.6%; P=.032). For the whole group, mortality rate was 3.2% (two patients in group RH-, and none in group RH+). Patients with liver resection had a longer postoperative stay (14.4 vs. 23.1 days) (P=.027). Median overall survival was 33 months for RH-, and 36 for RH+ group. Median disease-free survival was 16 months for RH-, and 24 months for RH+ group. CONCLUSIONS: Simultaneous peritoneal cytoreduction and hepatic resection resulted in a significantly higher Clavien grade III-V morbidity and a longer hospital stay, although the results are similar to other major abdominal interventions. The application of multimodal oncological and surgical treatment may obtain similar long-term survival results in both groups.